Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium.

Abstract

The mRNA for Rvp.1 (rat ventral prostate) increases in abundance before gland involution after androgen deprivation. Rvp.1 is homologous to CPE-R, the high-affinity intestinal epithelial receptor for Clostridium perfringens enterotoxin (CPE), and is sufficient to mediate CPE binding and trigger subsequent toxin-mediated cytolysis. Rvp.1 (claudin-3) and CPE-R (claudin-4) are members of a larger family of transmembrane tissue-specific claudin proteins that are essential components of intercellular tight junction structures regulating paracellular ion flux. However, claudin-3 and claudin-4 are the only family members capable of mediating CPE binding and cytolysis. The present study was designed to study the expression of claudin-3 and claudin-4 in human prostate tissue as potential targets for CPE toxin-mediated therapy for prostate cancer. On human multiple-tissue Northern blot analysis, mRNAs for both claudin-3 and claudin-4 were expressed at high levels in prostate tissue. In normal prostate tissue, expression of claudin-3 was localized exclusively within acinar epithelial cells by in situ mRNA hybridization. Compared with expression within prostate epithelial cells in surrounding normal glandular tissue, expression of claudin-3 mRNA remained high in the epithelium of prostate adenocarcinoma (10 of 10) and prostatic intraepithelial neoplasia (five of five). Prostate adenocarcinoma cells metastatic to bone were obtained from a patient with disease progression during antiandrogen therapy. These metastatic cells were prostate-specific antigen-positive by immunohistochemical staining and also expressed functional CPE receptors as measured by sensitivity to CPE-induced cell lysis. The persistent high level of claudin-3 expression in prostate adenocarcinoma and functional cytotoxicity of CPE in metastatic androgen-independent prostate adenocarcinoma suggests a new potential therapeutic strategy for prostate cancer.

• Authors: H Long, C D Crean, W H Lee, O W Cummings, T G Gabig
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 21 Pg. 7878-81 (Nov 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11691807 (Publication Type: Journal Article)

Chemical References

• Androgens
• CLDN3 protein, human
• CLDN4 protein, human
• Claudin-3
• Claudin-4
• Cldn3 protein, rat
• Enterotoxins
• Membrane Proteins
• RNA, Messenger
• enterotoxin, Clostridium

Topics

• Adenocarcinoma (drug therapy, metabolism, secondary)
• Androgens (physiology)
• Animals
• Bone Marrow Neoplasms (drug therapy, metabolism, secondary)
• Chlorocebus aethiops
• Claudin-3
• Claudin-4
• Clostridium perfringens (genetics, metabolism)
• Enterotoxins (metabolism, toxicity)
• Epithelial Cells (metabolism, pathology)
• Humans
• Male
• Membrane Proteins (biosynthesis, genetics)
• Neoplasms, Hormone-Dependent (drug therapy, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• RNA, Messenger (biosynthesis, genetics)
• Vero Cells